The proposed research concerns pathogenetic mechanisms in certain disorders of hematopoiesis and involves 3 areas of investigation. 1. Drug-induced bone marrow injury as exemplified by chloramphenicol (CAP)-induced marrow damage. Emphasis will be directed at the molecular mechanisms underlying the common reversible erythroid suppression from CAP and the more devastating complication of aplastic anemia. The nature of the mitochondrial lesion from CAP will be studied. Attempts will be made to uncover a predisposition in individuals susceptible to CAP aplastic anemia by studying the in vitro effect of the drug on bone marrow from patients who have recovered from this complication. 2. Studies on the regulation of granulopoiesis using in vitro culture techniques. Colony stimulating factor from human lung is being purified and characterized. Colony forming cells from human bone marrow are being studied as to their heterogeneity and responsiveness to different sources of colony stimulating factor. 3. Elucidate the role of cytoplasmic DNA and RNA polymerases in the regulation of gene expression in erythroid cells. This objective will be approached by further purification and characterization of these polymerases, their endogenous templates and their product from both, bone marrow erythroblasts and peripheral reticulocytes.